Over the past three decades there has been a strong focus in the field of addiction towards the development of vaccines for the prevention and treatment of tobacco smoking (nicotine dependence). Based on preclinical studies in rodents, the presumed mechanism of action is that the antibodies produced by vaccination, bind to nicotine and decrease the rate and the amount of nicotine that is able to cross the blood brain barrier and occupy nicotinic acetylcholine receptors (nAChR) in the mesocorticolimbic reward pathway. In the present study, we propose to validate this mechanism in living human smokers. Specifically, we will image brain 22 nAChR using the nicotinic agonist [123I]5 IA 85380 ([123I]5 IA) and single photon emission computed tomography (SPECT) to determine the amount of nicotine occupancy of brain 22 nAChR after an IV nicotine challenge in smokers before and after vaccination with the NicVax vaccine. We hypothesize that after vaccination, the amount of nicotine occupying 22 nAChR will be reduced by at least 50%. If confirmed, this reduction in the amount of nicotine occupying nAChR will explain why, vaccinated individuals will be less likely to become addicted if they smoke, and current smokers will not experience the same satisfaction from smoking.